RNA splicing antisense technology allows researchers to influence the ultimate structure and function of proteins. Proteins are synthesized from instructions coded in the DNA through a multi-step process that includes RNA splicing. Information stored in the DNA of genes is transcribed into immature "pre-messenger RNAs" (pre-mRNAs), pre-mRNAs are then spliced into mature "messenger RNAs" (mRNAs), and finally, mRNAs are translated into proteins. In humans and most other organisms, the splicing process thus ensures proper protein production.

"Targeting the splicing process is a promising strategy for finding new medicines to treat SMA, and possibly other diseases," said Marcus Rhoades, Ph.D. of the National Institute of General Medical Sciences, which partially supported Krainer's research. "This work brings us one step closer to that goal."

The defect in SMN2 gene expression in SMA patients is at the level of pre-mRNA splicing, such that exon 7 tends to be left out of the mRNA that ultimately makes SMN protein. Several strategies have been pursued to increase the extent of exon 7 inclusion in the splicing of SMN2, for eventual use as therapeutics for SMA. The Krainer team, in collaboration with a team at Isis Pharmaceuticals, surveyed a large number of antisense oligonucleotides (ASOs) and found that some of these ASOs are able to correct the mRNA splicing defect in cultured cells from SMA patients. These powerful ASOs are identified by the Krainer team as viable for testing in mouse models - the next step in the process of developing new human therapies.

"Families and advocates are very pleased to see the advancement of this antisense technology for the treatment of spinal muscular atrophy. We have high hopes for the success of the next phase of the work", said Cynthia Joyce, Executive Director of the SMA Foundation, an advocacy group that provides financial support for this project at CSHL.